A promising α-amylase inhibitor based on the 2-(2-hydrazinyl) thiazole scaffolds: synthesis, docking studies and biological evaluation

• Published in: Phosphorus, sulfur, and silicon and the related elements sulfur, and silicon and the related elements, 2024-09, Vol.199 (7-9), p.804-813
• Main Authors: Raut, Dattatraya, Bhosale, Dnyandev, Bhosale, Raghunath, Lawand, Anjana, Hublikar, Mahesh, Nirmal, Shraddha, Dhadake, Shailaja, Chaudhari, Praffula, Deshmukh, Sandip, Hiwarale, Dipak
• Format: Article
• Language: English
• Subjects: 2-(2-hydrazinyl) thiazole; Amylases; Antidiabetics; aromatic compounds; Binding sites; Cellular structure; Chemical synthesis; Diabetes; docking study; Mass spectrometry; Molecular docking; NMR; Nuclear magnetic resonance; pancreatic α-amylase protein; PEG-300; Scaffolds; Thiosemicarbazone; α-amylase inhibitors
• ISSN: 1042-6507; 1563-5325
• DOI: 10.1080/10426507.2024.2424274

A series of novel hydrazinyl-based thiazole scaffolds were designed, synthesized, and evaluated for their anti-diabetic activity. The cyclocondensation reaction of the appropriately substituted acetophenones 1, thiosemicarbazide 2, and appropriate phenacyl bromide 3 allowed for the creation of a new series of hydrazinyl-based thiazole scaffolds (4a-h). The newly generated compounds were characterized using mass spectrometry, 1 H NMR, IR, and 13 C NMR techniques. The novel hydrazinyl-based thiazole scaffolds were evaluated by the in vitro α-amylase inhibitory assay. Hydrazinyl-based thiazole scaffolds 4a, 4b, 4d, and 4f showed good activity compared to acarbose as a standard reference. Although insulin is a necessary medication for the treatment of diabetes, it carries a significant risk. We believe that thiazole scaffolds based on hydrazinyl structural motive provide recommendations for designing and producing novel anti-diabetic drugs, which are critically needed. Moreover, these compounds show a strong affinity for the pancreatic α-amylase protein binding site, suggesting greater inhibitory capability at the cellular level, and molecular docking studies have demonstrated their better-fit potential as anti-diabetic agents. This indicates the versatility of the hydrazinyl-based thiazole molecules to achieve new classes of anti-diabetic scaffold.